Under this ADAMHA grant, the Scripps-Salk-UCSD-San Diego State University Alcohol Research Center (SSU-ARC) proposes to continue its long term, cooperative, interdisciplinary research focussed on the theme of "CNS Effects of Alcohol". For this renewal application, the SSU-ARC will consist of 9 Components: The Administrative Core resource (supervising 3 supporting resource units), 8 independent collaborating research Components as well as a separate Pilot Project Component, supervised by the Administrative Core designed to stimulate new directions and recruit new investigators to ethanol centered research. The SSU-ARC research program remains strongly interdisciplinary, employing molecular, cellular, systematic and behavioral research methods on human and experimental animal subjects. Three major subthemes emerging from our past 14 yrs of work within this Center will be continued: 1) the molecular and cellular mechanisms of short term ethanol intoxication, and its endocrine, metabolic and behavioral concomitants 2) the molecular, cellular and behavioral changes underlying alcohol neurotoxicity on chronic exposure to ethanol (including aversive behavioral changes) in the adult and developing rodent and human nervous system, such as the Fetal Alcohol Syndrome; 3) the molecular, cellular and neuropsychological basis for susceptibility to alcoholism in humans, including the re- inforcing actions of ethanol. Individual research components range from studies of molecular genetic neuronal development through radiological and electrophysiological analysis of human FAS neuropathology, cellular and intracellular indices of intoxication, neuronal and endocrine indices of tolerance, dependence and toxicity. The Center also supports a participating unit in the NIAAA sponsored Consortium on the Genetics of Alcoholism, as well as other Center-funded, and RO-1 funded research on human CNS indices of short term and long term ethanol sensitivity. Research funded within this Center provides knowledge which will reduce the burden of illness associated with the consequences of alcohol abuse, and help define factors than can reduce the susceptibility to, and thereby prevent, alcohol abuse and alcoholism.